Intrinsic ability of GM + IL-4 but not Flt3L-induced rat dendritic cells to promote allogeneic T cell hyporesponsiveness

Abstract The influence of GM + IL-4 and Flt3 ligand (FL) on phenotype and function of BM-derived DC from Lewis rats was investigated. GM + IL-4-induced DC, despite expression of CD80/CD86, were less stimulatory than FL-induced DC that expressed low CD80/CD86 and were efficient stimulators of allogeneic T cells. GM + IL-4 DC were CD11b+ OX62lo , whereas FL DC were CD11blo OX62+ . Following activation, GM + IL-4 DC produced IL-10 and IL-6, but no IL-12p70, and were resistant to further maturation. FL DC produced IL-12p70, IFN-α/β, IL-10 and IL-6 and underwent maturation. Repeated stimulation of T cells with GM + IL-4 DC inhibited proliferation, cytokine production and induced early T cell apoptosis. FL DC-activated T cells produced large amounts of IFN-γ/IL-10 and exhibited late T cell apoptosis/necrosis. In vivo, GM + IL-4 DC induced alloAg-specific hyporesponsiveness following T cell restimulation. These results demonstrate that GM + IL-4 DC display intrinsic regulatory properties, inducing passive-cell-death in T cells with potential for inactivation/regulation of alloreactive T cells in transplantation.